Background: The ectoparasitic mite, Varroa destructor, is considered to be one of the most significant threats to apiculture around the world. Chemical cues are known to play a significant role in the host-finding behavior of Varroa. The mites distinguish between bees from different task groups, and prefer nurses over foragers. We examined the possibility of disrupting the Varroa – honey bee interaction by targeting the mite's olfactory system. In particular, we examined the effect of volatile compounds, ethers of cis 5-(2′-hydroxyethyl) cyclopent-2-en-1-ol or of dihydroquinone, resorcinol or catechol. We tested the effect of these compounds on the Varroa chemosensory organ by electrophysiology and on behavior in a choice bioassay. The electrophysiological studies were conducted on the isolated foreleg. In the behavioral bioassay, the mite's preference between a nurse and a forager bee was evaluated. Principal findings: We found that in the presence of some compounds, the response of the Varroa chemosensory organ to honey bee headspace volatiles significantly decreased. This effect was dose dependent and, for some of the compounds, long lasting (>1 min). Furthermore, disruption of the Varroa volatile detection was accompanied by a reversal of the mite's preference from a nurse to a forager bee. Long-term inhibition of the electrophysiological responses of mites to the tested compounds was a good predictor for an alteration in the mite's host preference. Conclusions: These data indicate the potential of the selected compounds to disrupt the Varroa - honey bee associations, thus opening new avenues for Varroa control.